Alcohols, amino polymer-bound

The polymer-bound catalysts A-C. (Table 31) are prepared by reaction of the corresponding amino alcohols with partially chloromethylated 1 -2% cross-linked polystyrene. In the case of A, the enantioselectivity of the addition of dialkylzincs to aldehydes is higher than with the corresponding monomeric ephedrine derivatives (vide supra). Interesting insights into the mechanism of the alkylation of aldehydes by dialkylzinc reagents can be obtained from the experi-... 

Various polymer-bound (polystyrene-bound) oxazaboroHdine catalysts for the reduction of secondary alcohols were reported [128]. These can simply be prepared by condensation of the resin-bound boronic acid with chiral 1,2-amino alcohols. The best results as far as enatioselectivity is concerned were obtained with oxaza-borohdine (59) (Scheme 4.36). 

Scheme 13) (35). This high selectivity can be obtained with the 1 2 amino alcohol-borane reagent, however, the 1 1 reagent is less reactive and affords only low stereoselectivity (36). The continuous-flow reaction using a polymer-bound amino alcohol provides evidence for the catalytic nature of the reduction with respect to the chiral ancillary. The reduction is accelerated by the presence of the amino alcohol-borane adduct, and the product is not bound to the complex. 

Furthermore, it is reported that metal catalysts usually require a basic pH for sufficient activity for the aerobic oxidation of alcohols in water [85]. Thus, Biffis found that the productivity of the Au nanoclusters can be enhanced by running the reaction at basic pH (pH 9.9) in their system. However, further enhancement of the pH of the reaction solution was not possible, due to the precipitation of catalyst caused by the increased hydrophobicity of the microgel through deprotonation of the polymer-bound amino groups [84]. In our work, we tried to carry out the catalytic reaction... 

Polymer-bound isonitrile (423), obtained from TentaGel-NH2 through treatment of the resin with formic acid and acetic anhydride, followed by dehydration of the resulting formamide with tosyl chloride and pyridine, has been employed in the preparation of N-substituted amino add ester [349]. Thus, Ugi MCR, performed in the presence of an alcohol instead of the carboxylic component, gave rise to an imino-ether spedes (426). Several Lewis acids were tested in searching for optimal reaction conditions. Boron trifluoride etherate displayed the better yields in term of desired product of the Ugi-type reaction. Amino acid methyl esters (427) were thus obtained when using methanol as the alcohol component, after deavage from the resin of the intermediate imino-ethers by an acetone/water mixture (Scheme 87). 

To allow for a diverse multi-step synthesis, we transformed the 3-hydroxy-2-methyl-idene propionic acids (Fig. 6.9) into polymer-bound allylic amines, which can be considered as unusual (3-amino acid derivatives. The polymer-bound allylic alcohols were first treated with acetyl chloride and DIEA in CH2C12 to form the ester, which was reacted with primary amines in an addition elimination step to form allylic amines. 

The mechanisms that have been proposed for the amino alcohol-catalyzed reaction all involve two zinc atoms, one amino alcohol and three alkyl groups on the active catalyst [65,71-74]. A composite mechanism is illustrated in Scheme 4.5 for a generic P-amino alcohol. NMR evidence [71] indicates dynamic exchange of the alkyl groups on zinc as shown in the brackets (a bridged species has also been proposed [71]). In experiments done with a polymer-bound amino alcohol catalyst, Frechet has noted that the alkoxide product is not bound to the catalyst and that the alkyl transfer must have therefore occured from diethylzinc in solution. 

Many supported or heterogeneous catalysts used for Diels-Alder reactions are known to give better results than their non-supported analogues. Nevertheless, chiral catalysts for asymmetric Diels-Alder reactions are scarce. Mayoral, Luis and coworkers studied the use of a variety of chiral polymer-bound amino alcohols as catalysts in cycloaddition reactions. Reaction of cyclopentadiene with methacrolein in the presence of (S)-prolinol-derived resin 81 proceeded with excellent yield (98%) but poor enantioselectivity (14% e.e.) as shown in Scheme 3.6.8. Once again, extrapolation from solution phase chemistry to a solid-supported reaction proved difficult. 

A solid-phase method for the synthesis of optically active esters has been developed, which involves the alkylation of the polymer-bound oxazoline (34) (Scheme 26). An optical yield of 56% with chemical yields between 43 and 48% are obtained the polymer-bound amino-alcohols may be reisolated and used again. 

Nicolaou et al. have prepared a library of 22 Sarcodictyin-analogs by attaching core structure 2 onto solid phase using polymer-bound Wittig-ylide 1 (Scheme 1) [74]. The OH-groups of the core scaffold were decorated by alkylation or converted to carboxylic acid or amino functionalities which could be derivatized as esters, carbamates, or secondary amines. Cleavage off the soUd phase was performed via trans-ketalization, a reaction step which was exploited to increase the diversity by using different kind of alcohols. 

Metal ion complexes. These classic CSPs were developed independently by Davankov and Bernauer in the late 1960s. In a typical implementation, copper (II) is complexed with L-proline moieties bound to the surface of a porous polymer support such as a Merrifield resin [28-30]. They only separate well a limited number of racemates such as amino acids, amino alcohols, and hydroxy acids. 

In 1982 Cardillo used a three-step sequence involving two supported reagent systems to convert /i-iodoamines into amino alcohols (Scheme 2.23) [45]. Polymer-supported acetate ions were used for the substitution of the iodide which immediately underwent acyl transfer to the amine. The resulting compound (10) was directly treated with hydrochloric acid to cleave the amide and the free base was subsequently obtained from the reaction by treatment with a resin-bound carbonate. This was of particularly synthetic value because of the high water solubiHty of these amino alcohol compounds that would have made aqueous work-up challenging. 

Yashima and co-workers reported the memory of macromolecular helicity of poly((4-carboxyphenyl)acetylene) (poly-98). Poly-98 itself possesses a large number of short helical units with many helix-reversal points, and is therefore achiral. However, in the presence of optically active amine 99, which can interact with the polymer s carboxyl groups, one-handed macromolecular helicity is induced in the polymer. When achiral amino alcohol 100 is added to the helical complex, chiral amine 99 bound to poly-98 is replaced by stronger base 100. Nevertheless, the newly formed complex still shows a one-handed helical conformation. Even after the removal of 99 by gel permeation chromatography, the poly-98-100 complex retains a one-handed helical conformation without a loss of helical intensity. Thus the helicity of poly-98 induced by complexation with a chiral amine was memorized after replacement by an achiral one. The half-life of the chiral memory is as long as four years at room temperature.48... 

Like conventional solid supports, soluble polymers may have a potential to function as scavengers in solution-phase synthesis. The approach has been applied to the synthesis of p-amino alcohols that are structurally related to propranolol. The crude products (prepared from the corresponding epoxides and amines) and an added PEG-bound borohy-dride reagent formed a complex which was precipitated and separated from unreacted starting materials and unwanted by-products. Cleavage with HC1 in MeOH/DCM and precipitation of the polymer gave a solution of pure (>92%) p-amino alcohols [75]. 

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